bims-supasi 2025-11-09 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2025–11–09
fourteen papers selected by
Jonathan Wolf Mueller, University of Birmingham

Oral efficacy of structurally defined chondroitin sulfate Co-administered with SNAC in Parkinson's disease.
Genistein and 17β-Estradiol Inhibit Extracellular Matrix Production and Chondroitin Sulfate Synthesis in ATDC5 Cells.
Impact of genetic polymorphisms on the sulfation of dehydroepiandrosterone and 17-β estradiol by human cytosolic sulfotransferase SULT2B1a.
Leukocytes have a heparan sulfate glycocalyx that regulates recruitment during psoriasis-like skin inflammation.
Low dose NSAIDs and sysadoas in the management of knee osteoarthritis.
Sulfonation Disposition of Capsaicin: In Vitro and in Vivo.
A highly biocompatible polyethyleneimine/sulfonated polysulfone hemoperfusion microsphere with tailored surface charge for rapid and efficient removal of major protein-bound uremic toxins from simulated human plasma.
Recombinant Yeast Platform for Production and Verification of Diverse Quercetin Heteroconjugates.
Kidney clearances of protein-bound uremic toxins predict outcomes in chronic kidney disease: a prospective cohort study.
Structure-Guided Engineering of Human 3'-Phosphoadenosine-5'-phosphosulfate Synthetase 1 to Enhance Biosynthesis of PAPS.
Extravesicular Chloride Ion Regulates the Uptake of ATP, Sulfate, and Inorganic Phosphate by Membrane Vesicles from Bovine Adrenal Chromaffin Granules.
Sulfotransferase SULT2B1 contributes to the epithelial-immune microenvironment homeostasis in imiquimod-induced psoriatic dermatitis.
Liver fibrosis is associated with men's health care symptoms, especially erectile dysfunction and lower urinary tract symptoms.
Fetal Dehydroepiandrosterone from Hair Samples at Birth Predicts Language Development.

Carbohydr Polym. 2026 Jan 01. pii: S0144-8617(25)01276-7. [Epub ahead of print]371 124492

Oral efficacy of structurally defined chondroitin sulfate Co-administered with SNAC in Parkinson's disease.

Ying Guo, Bin Zhang, Changkai Bu, Zizhe An, Deling Shi, Lan Jin, Anran Sheng, Aihua Zhen, Lianli Chi.

  Parkinson's disease (PD) is a progressive neurodegenerative disorder with limited therapeutic options and suboptimal long-term efficacy. Although glycosaminoglycans such as chondroitin sulfate (CS) possess neuroprotective potential, their clinical application is hampered by poor oral bioavailability and limited target specificity. In this study, we first established a highly sensitive LC-MS/MS MRM assay to quantify CS in plasma. Using animal models, we demonstrated that co-administration with N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) significantly enhanced the oral bioavailability of CS compared to deoxycholic acid (DOCA) modification. Subsequently, we synthesized a structurally defined 6-O-desulfated chondroitin sulfate octasaccharide (CS-dp8-de6S) and evaluated its therapeutic efficacy in MPTP-induced PD mouse models via co-administration with SNAC. Treatment with CS-dp8-de6S/SNAC improved motor performance in the pole and hanging tests, partially restored striatal dopamine levels, and upregulated tyrosine hydroxylase expression in the substantia nigra, these effects were significantly greater than those observed with non-desulfated CS-dp8, demonstrating its enhanced specificity. Mechanistic studies using gel mobility shift assay and dual immunohistochemistry revealed that CS-dp8-de6S treatment effectively reduced pathological fibrinogen β-chain (FGB) deposition in brain tissues. These findings highlight the potential of structurally defined CS oligosaccharides as novel disease-modifying therapeutics for PD and provide a basis for the development of carbohydrate-based strategies targeting proteinopathies in neurodegenerative disorders.

Keywords:  6-O-desulfated chondroitin sulfate octasaccharide; Fibrinogen β-chain; Oral administration; Parkinson's disease

DOI:  https://doi.org/10.1016/j.carbpol.2025.124492
J Nutr Sci Vitaminol (Tokyo). 2025 ;71(5): 456-466

Genistein and 17β-Estradiol Inhibit Extracellular Matrix Production and Chondroitin Sulfate Synthesis in ATDC5 Cells.

Seika Takeda, Kae Warita, Aki Fujiwara, Chisaki Asatsuma, Yuki Saito-Matsuzawa, Kota Shiozawa, Hideyuki Sone, Shin Kamiyama.

  Genistein is one of the most estrogenic soy isoflavones. This study investigated the effects of genistein and 17β-estradiol (E2) on early chondrogenesis and extracellular matrix (ECM) production in chondrogenic ATDC5 cells. At low concentrations, E2, but not genistein, enhanced chondrogenic differentiation. Higher concentrations of E2 and genistein suppressed ECM production and expression of genes involved in chondroitin sulfate (CS) proteoglycan synthesis, including aggrecan core protein, CS synthases, 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthases, PAPS transporters, and CS sulfotransferases. Genistein exerted a stronger inhibitory effect than E2 and completely abolished the increase in Tgfb1 gene expression during chondrogenic differentiation. Treatment with estrogen receptor antagonist ICI 182780 did not inhibit E2- or genistein-dependent inhibition of chondrogenesis. Furthermore, E2 and genistein exhibited equivalent partial inhibition of transforming growth factor beta (TGF-β)-induced upregulation of Acan and Col2a1 expression. These results indicate that the inhibitory effects of high concentrations of E2 and genistein are dependent on TGF-β, but not the estrogen receptor pathway.

Keywords:  ATDC5; TGF-β; chondroitin sulfate; estrogen; extracellular matrix; genistein; soy isoflavone

DOI:  https://doi.org/10.3177/jnsv.71.456
Pharmacogenet Genomics. 2025 Nov 05.

Impact of genetic polymorphisms on the sulfation of dehydroepiandrosterone and 17-β estradiol by human cytosolic sulfotransferase SULT2B1a.

Eid Alatwi, Ahsan F Bairam.

   BACKGROUND: Dehydroepiandrosterone (DHEA) is considered an endogenous steroid hormone precursor, and 17-ß estradiol (E2) is one of the estrogen steroid hormones. Of the 13 known human cytosolic sulfotransferases (SULTs), SULT2B1a has been shown to be expressed in steroid hormone-responsive tissues such as the prostate, ovary, and placenta, as well as the fetal brain. Previous studies have demonstrated that SULT2B1a is capable of sulfating 3β-hydroxysteroids such as DHEA and pregnenolone. The present study aimed to investigate the effects of human SULT2B1 single-nucleotide polymorphisms (SNPs) on the enzymatic characteristics of SULT2B1a allozymes in mediating the sulfation of DHEA and E2.
METHODS: To inspect the effects of SNPs of the SULT2B1 gene on the sulfation of DHEA and E2 by SULT2B1a allozymes, 13 recombinant SULT2B1a allozymes were produced, expressed, and purified using established procedures. Thirteen SULT 2B1a nonsynonymous missense coding SNPs (cSNPs) were selected among numerous identified human SULT 2B1a SNPs by a comprehensive database search. The corresponding cDNAs, packaged in pGEX-2TK expression vector, and encoding the selected 13 SULT2B1a allozymes, have been generated by performing site-directed mutagenesis. These were then bacterially expressed in BL21 E. coli cells and purified using glutathione-Sepharose affinity chromatography. The purified allozymes were tested for their ability to sulfonate DHEA and E2.
RESULTS: In terms of the kinetic parameters, the wild-type SULT2B1a exhibited higher enzyme affinity toward DHEA than with E2. In comparison with the wild-type SULT2B1a, the purified allozymes displayed differential sulfating activities toward DHEA and E2.
CONCLUSION: Accordingly, these findings indicate an apparent effect of SULT2B1 cSNPs on the sulfating activities of SULT2B1a allozymes toward DHEA and E2, and may provide for a better understanding of the pharmacokinetics of DHEA and E2 in individuals with differing SULT2B1a genotypes.

Keywords:  DHEA; E2; SNPs; SULT2B1a; sulfation

DOI:  https://doi.org/10.1097/FPC.0000000000000561
Sci Signal. 2025 Nov 04. 18(911): eadr0011

Leukocytes have a heparan sulfate glycocalyx that regulates recruitment during psoriasis-like skin inflammation.

Megan J Priestley, Anna K Hains, Iashia Z Mulholland, Sam Spijkers-Shaw, Joshua C Müller, Gareth Howell, Amanda J L Ridley, H Davies-Strickleton, Rebecca L Miller, Max Nobis, Olga V Zubkova, Amy E Saunders, Douglas P Dyer.

The glycocalyx is a proteoglycan-rich layer present on the surface of all mammalian cells and is particularly prevalent on endothelial cells lining the vasculature. The glycocalyx is thought to affect leukocyte migration by masking adhesion molecules and reducing leukocyte adhesion to the endothelium. Leukocyte recruitment is a key driver of inflammatory diseases, including psoriasis. Here, we found that leukocytes had the glycocalyx component heparan sulfate on their cell surface and that it was lost in response to psoriasis-like skin inflammation. In contrast, endothelial heparan sulfate was not affected. Treatment with a heparan sulfate mimetic during psoriasis-like skin inflammation in mice protected heparan sulfate from cleavage by myeloid cell-derived heparanase and resulted in reduced leukocyte accumulation in the skin. However, clinical signs of inflammation were increased because of the reduced numbers of T regulatory cells that were recruited. These findings refine our understanding of immune cell recruitment by revealing the presence and function of a heparan sulfate glycocalyx on immune cells and highlight the complex effects of heparanase inhibitors on the immune response in this context.

DOI: https://doi.org/10.1126/scisignal.adr0011
Aging Clin Exp Res. 2025 Nov 06. 37(1): 317

Low dose NSAIDs and sysadoas in the management of knee osteoarthritis.

Alberto Migliore, Orazio De Lucia, Alessandro de Sire, Andrea Šajbidor, Ladislav Šenolt, Sándor Szántó, Joan Calvet Fontova, Johannes Flechtenmacher, Ali Mobasheri, Jordi Monfort Faure, Jean-Yves Reginster, Nicola Veronese.

   INTRODUCTION: Osteoarthritis (OA) is a chronic, progressive joint disease characterized by the degradation of articular cartilage, subchondral bone remodeling, synovial inflammation, and osteophyte formation. Despite being a leading cause of disability in older people, effective long-term management of OA remains a significant challenge. Current treatment strategies primarily focus on symptom control, with both non-pharmacological and pharmacological interventions.
MATERIALS AND METHODS: A systematic literature review followed by a structured Delphi survey was conducted, involving an international Technical Expert Panel (TEP) of OA specialists. The panel evaluated the efficacy, safety, and clinical utility of combining low dose diclofenac and chondroitin sulfate in OA management.
RESULTS: The analysis of expert consensus indicated that the combination of low dose diclofenac and chondroitin sulfate may be effective in reducing pain and improving joint function in patients with knee OA. Additionally, this combination could reduce the need for higher doses of NSAIDs, thereby minimizing systemic adverse effects.
CONCLUSION: The combination of low dose diclofenac and chondroitin sulfate represents a promising therapeutic strategy for managing knee OA. Further studies are needed to confirm these findings and optimize therapeutic strategies to improve patient outcomes.

Keywords:  Chondroitin sulfate; Diclofenac; Knee osteoarthritis; Low dose diclofenac; NSAIDs; Osteoarthritis

DOI:  https://doi.org/10.1007/s40520-025-03221-2
J Med Chem. 2025 Nov 04.

Sulfonation Disposition of Capsaicin: In Vitro and in Vivo.

Xiaohuan Dou, Shan Wang, Qidong Zhang, Jian Mao, Guobi Chai, Qingzhao Shi, Yunhe Zhu, Wu Fan.

Capsaicin (CAP), the major pungent component of chili peppers, undergoes sulfation mediated by sulfotransferases (SULTs), an important phase II metabolic pathway influencing its pharmacological properties. In this study, we systematically investigated the sulfation metabolism of CAP and its underlying mechanisms in vitro and in vivo. Five sulfated metabolites were identified in rats with the liver as the primary site. Among them, M3-SO3 was the most abundant, followed by CAP-SO3 and M2-SO3, while M4-SO3 was the least abundant. SULT1C4 and SULT1E1 mainly catalyzed CAP and M2 sulfation, whereas SULT1C4 was essential for M3 sulfation. In addition, CAP sulfation occurred in multiple brain regions. Unlike the liver, brain metabolism favored M2-SO3 over M3-SO3, highlighting distinct central versus peripheral sulfation profiles. Brain microdialysis further confirmed this discrepancy. These findings provide a foundation for exploring the pharmacological roles of CAP and its sulfated metabolites, particularly within the central nervous system.

DOI: https://doi.org/10.1021/acs.jmedchem.5c01670
Regen Biomater. 2025 ;12 rbaf082

A highly biocompatible polyethyleneimine/sulfonated polysulfone hemoperfusion microsphere with tailored surface charge for rapid and efficient removal of major protein-bound uremic toxins from simulated human plasma.

Shujing Wang, Jiahao Liang, Yu Chen, Xianda Liu, Dongmei Tong, Yupei Li, Weifeng Zhao, Baihai Su, Changsheng Zhao.

  Conventional hemodialysis and hemodiafiltration prove less effective at removing protein-bound uremic toxins (PBUTs) from the bloodstream of end-stage renal disease patients, primarily because PBUTs cannot pass through the small pores in the polymeric membranes. Hemoperfusion is an extracorporeal blood purification technique that employs an adsorption mechanism to remove multiple uremic toxins from such patients. Yet, the efficacy of hemoperfusion is constrained by some limitations of contemporary adsorbents, such as suboptimal capacity to adsorb PBUTs and poor hemocompatibility, presenting significant barriers for their clinical application. To address these challenges, we engineered a tailored hemoperfusion adsorbent by compounding sulfonated polysulfone (SPSf) and polyethyleneimine (PEI) into polyethersulfone (PES) microspheres to effectively capture and remove PBUTs through electrostatic interactions. Specifically, we introduced sulfuric acid into the coagulation bath to increase the adsorption amount of the developed adsorbent (H-PES/SPSf@PEI microspheres), to neutralize strong positive charge of PEI and to improve hemocompatibility. The tailored H-PES/SPSf@PEI microspheres neither damage blood cells nor activate the complement pathway when they contact with human blood. Moreover, H-PES/SPSf@PEI microspheres have a high adsorption amount toward major PBUTs, including hippuric acid (HA, 34.24 mg/g), 3-indoleacetic acid (IAA, 49.19 mg/g), p-cresol sulfate (PCS, 40.31 mg/g) and indoxyl sulfate (IS, 128.67 mg/g) by fitting adsorption isotherms. In a simulated hemoperfusion setting, the removal ratio of IS, IAA, PCS and HA by H-PES/SPSf@PEI microspheres reaches nearly 75.33%, 41.73%, 44.36% and 21.11%, respectively, with 47.89% of IS, 40.64% of IAA, 44.42% of PCS and 37.35% of HA being removed from BSA solution. In conclusion, H-PES/SPSf@PEI microspheres hold a potential to eliminate PBUTs from patients with end-stage renal disease.

Keywords:  adsorption; electrostatic interactions; hemocompatibility; hemoperfusion; protein-bound uremic toxins

DOI:  https://doi.org/10.1093/rb/rbaf082
J Agric Food Chem. 2025 Nov 04.

Recombinant Yeast Platform for Production and Verification of Diverse Quercetin Heteroconjugates.

Mst Julia Sultana, Miyu Nishikawa, Yui Sudaka, Shinichi Ikushiro.

  Flavonoids, such as quercetin, are extensively metabolized, producing glucuronide, sulfate, and heteroconjugate derivatives that influence their bioavailability and biological effects. In this study, we investigated quercetin heteroconjugation using recombinant yeast systems, engineered to express uridine diphosphate-glucuronosyltransferases and sulfotransferases. This strategy was inspired by the observation of diverse heteroconjugate profiles produced by hepatic and intestinal S9 fractions from both rats and humans, highlighting the metabolic complexity of quercetin biotransformation. The yeast-based in vitro platform successfully facilitated the biosynthesis of structurally distinct heteroconjugates, notably Q7G/4'S, Q3G/4'S, Q7G/3'S, and Q3G/3'S, under controlled conditions. The regioselective nature of heteroconjugation was rigorously validated through targeted enzymatic deconjugation using β-glucuronidase and sulfatase, followed by detailed chromatographic analysis, to ensure precise structural confirmation. This integrated approach underscores the robustness of coupling enzymatic assays with high-performance liquid chromatography profiling to verify complex conjugate structures. Collectively, these findings demonstrate the effectiveness of a yeast-based quercetin heteroconjugate biotransformation approach.

Keywords:  UDP-glucuronosyltransferase; enzymatic deconjugation; quercetin heteroconjugates; sulfotransferase; yeast-based biotransformation

DOI:  https://doi.org/10.1021/acs.jafc.5c10497
Ren Fail. 2025 Dec;47(1): 2578418

Kidney clearances of protein-bound uremic toxins predict outcomes in chronic kidney disease: a prospective cohort study.

Danshu Xie, Mengdi Jiang, Jiaolun Li, Yingjie Chen, Feng Ding, Wenji Wang.

  This prospective cohort study investigated the kidney clearance of protein-bound uremic toxins (PBUTs)-specifically, indole sulfate (IS), p-cresol sulfate (pCS), and indole-3-acetic acid (IAA)-across various stages of chronic kidney disease (CKD) stages and their associations with adverse clinical outcomes. From July 2018 to December 2020, 186 non-dialysis CKD patients were enrolled and followed until June 2025. Serum and 24-hour (24 h) urine PBUT levels were measured, and kidney clearances were analyzed. The findings indicated a decrease in the 24 h kidney clearances of IS (Cis), pCS (Cpcs), and IAA (Ciaa) corresponding with a reduction in glomerular filtration rate (GFR) across the CKD stages. For instance, the clearance of indoxyl sulfate was observed to decline from 26.7 mL/min in stage 1 to 2.2 mL/min in stage 5. PBUT clearances and fractional clearances were generally unaffected by 24 h urinary protein levels, with the exception of fractional clearance of IAA. Elevated levels of Cis and Ciaa were independently correlated with decreased risks of renal outcomes (IS: HR 0.964; IAA: HR 0.941) and hospitalization (IS: HR 0.984; IAA: HR 0.961). The study concluded that the 24 h kidney clearances of IS and IAA are independently associated with renal adverse outcomes and hospitalization, with minimal influence from urinary protein excretion.

Keywords:  Protein-bound uremic toxins; chronic kidney disease; kidney clearance; outcomes

DOI:  https://doi.org/10.1080/0886022X.2025.2578418
J Agric Food Chem. 2025 Nov 06.

Structure-Guided Engineering of Human 3'-Phosphoadenosine-5'-phosphosulfate Synthetase 1 to Enhance Biosynthesis of PAPS.

Ruixue Zhang, Jiajun Huang, Jiali Gu, Dongchao Xie, Jinsong Zhao, Lu Wang, Peng Jin.

  3'-Phosphoadenosine 5'-phosphosulfate (PAPS) is the essential sulfate donor for sulfation modifications in crucial biomolecules. Human bifunctional 3'-phosphoadenosine-5'-phosphosulfate synthase 1 (hPAPSS1) directly synthesizes PAPS in two sequential steps, circumventing the inefficiencies of multienzyme systems. However, unsatisfactory ATP substrate affinity and catalytic activity restrict its applications in the biosynthesis of sulfonyl compounds. Herein, a semirational design strategy was employed to enhance its activity, resulting in a positive combinatorial variant, hPAPSS1-C207G/F560W, which exhibited a 2.22-fold increase in activity and achieved a PAPS conversion rate of 34.45%. Molecular dynamics simulations revealed that the C207G substitution enhanced the flexibility of the C-loop, thereby improving its turnover rate. Concurrently, the F560W mutation optimized the conformations of key residues and reduced the binding free energy, enhancing its binding affinity for ATP. This study uncovered two bottleneck issues in enzyme activity and demonstrated mechanisms underlying the hPAPSS1 catalytic performance, enabling efficient synthesis of PAPS.

Keywords:  PAPS; hPAPSS1; molecular dynamics simulation; semirational design strategy

DOI:  https://doi.org/10.1021/acs.jafc.5c07712
J Biol Chem. 2025 Nov 04. pii: S0021-9258(25)02744-9. [Epub ahead of print] 110892

Extravesicular Chloride Ion Regulates the Uptake of ATP, Sulfate, and Inorganic Phosphate by Membrane Vesicles from Bovine Adrenal Chromaffin Granules.

Yoshinori Moriyama, Seiji Nomura, Sawako Moriyama, Nao Hasuzawa, Masatoshi Nomura.

  ATP stored in secretory vesicles is released into the extracellular space through exocytosis, acting as an intercellular messenger in purinergic signaling. The vesicular nucleotide transporter (VNUT) is crucial for filling the vesicles with ATP. However, the mechanisms that regulate this transport are not yet fully understood. This study explores how anions influence ATP uptake in membrane vesicles from the bovine adrenal chromaffin granules. Our findings indicate that ATP uptake is driven by the membrane potential established by the vacuolar H+-ATPase and is sensitive to diisothiocyanostilbene disulfonic acid, phosphoenolpyruvate, atractyloside and 2'(or-3')-O-(N-Methylanthraniloyl) adenosine 5'-triphosphate (MANT-ATP). Notably, extravesicular Cl- significantly influences the ATP uptake: facilitation of ATP uptake occurs at millimolar Cl- concentrations, peaking between 5-20 mM, although it declines sharply at higher Cl- levels. A considerable amount of ATP is taken up by nigericin plus K+ without Cl-. The membrane vesicles took up radiolabeled Cl- in an ATP- and membrane potential-dependent fashion, which is partially sensitive to 5-nitro-2-(3-phenylpropylamino)benzoic acid and MANT-ATP but not to AMP. Sulfate and inorganic phosphate (Pi) at mM levels inhibit ATP uptake and are taken up in an ATP-dependent manner, exhibiting similar energetics, Cl- dependency, and pharmacological profile to ATP uptake. In the mouse adrenal gland membranes, the uptake of sulfate and Pi depended on ATP, while this is not the case for those from VNUT knockout mice. These results suggest that VNUT transports not only nucleotides but also inorganic oxyanions, utilizing Cl- as a regulatory factor rather than an essential component of its activity.

Keywords:  Chloride ion; Chromaffin granule; Inorganic phosphate; Phosphoenolpyruvate; SLC17A9; Sulfate; VNUT; Vacuolar H(+)-ATPase

DOI:  https://doi.org/10.1016/j.jbc.2025.110892
Front Immunol. 2025 ;16 1632426

Sulfotransferase SULT2B1 contributes to the epithelial-immune microenvironment homeostasis in imiquimod-induced psoriatic dermatitis.

Kenji Morino, Sayaka Akiyoshi, Keisuke Matsubara, Yuki Sugiura, Yoshihiro Izumi, Shu Yotsumoto, Kazuhiko Yamamura, Rae Maeda, Masatomo Takahashi, Keisuke Nakata, Takeshi Bamba, Takeshi Nakahara, Daiji Sakata, Takehito Uruno, Yoshinori Fukui, Kazufumi Kunimura.

   Introduction: Skin protects the body from external threats by constituting an epithelial-immune microenvironment. Sulfotransferase family 2B member 1 (SULT2B1) converts cholesterol to cholesterol sulfate (CS). We previously reported that CS acts as an endogenous dedicator of cytokinesis 2 (DOCK2)-inhibitory metabolite suppressing immune cell migration and activation by inhibiting DOCK2-mediated Rac activation. Despite being located in the epidermis, pathophysiological roles of CS in cutaneous inflammation remain unknown.
Methods: We evaluated the Sult2b1-producing cells in the dorsal skin of wild-type mice and compared the degree of cutaneous inflammation between wild-type and Sult2b1 knockout mice using a psoriatic dermatitis model induced by topical imiquimod (IMQ). We also examined SULT2B1 gene expression levels in human epidermal keratinocytes to assess the effects of pro-inflammatory cytokines.
Results: Sult2b1 expression levels and CS production gradually increased in the skin of psoriatic dermatitis model mice. IMQ-induced dermatitis and neutrophil recruitment were exacerbated in the Sult2b1 knockout mice with a complete loss of CS. Furthermore, genetic deletion of Dock2 or intravenous administration of neutrophil-depleting antibodies alleviated IMQ-induced dermatitis in Sult2b1 knockout mice. Notably, CS was more abundant in the skin samples of patients with psoriasis than in the healthy control samples. Primary normal human epidermal keratinocytes exhibited significantly elevated SULT2B1 levels after Th1 cytokine treatment.
Discussion: These findings suggest that increased SULT2B1 levels in the skin under psoriatic conditions may be involved in a negative feedback mechanism that helps to limit excessive skin inflammation, thereby potentially contributing to the maintenance of epithelial-immune microenvironment homeostasis. Overall, our results raise the possibility that SULT2B1 plays an important role in cutaneous inflammation and could serve as a useful indicator or potential target in psoriasis.

Keywords:  DOCK2; SULT2B1; cholesterol sulfate; neutrophils; psoriasis; skin inflammation

DOI:  https://doi.org/10.3389/fimmu.2025.1632426
Investig Clin Urol. 2025 Nov;66(6): 551-558

Liver fibrosis is associated with men's health care symptoms, especially erectile dysfunction and lower urinary tract symptoms.

Yuka Uesaka, Akira Tsujimura, Riho Kasai, Yukiko Ota, Takashi Kanda, Yuta Anno, Haruhiko Wakita, Keisuke Ishikawa, Ayumu Taniguchi, Taiji Nozaki, Masato Shirai, Kazuhiro Kobayashi, Shigeo Horie.

   PURPOSE: The prevalence of liver dysfunction among men has been steadily increasing in recent decades. Among the various non-invasive assessment tools available, the Fibrosis-4 (FIB-4) Index has emerged as a particularly valuable and widely adopted scoring system for evaluating liver fibrosis. This study investigated the relationship between liver fibrosis evaluated by the FIB-4 Index and male health care parameters.
MATERIALS AND METHODS: Participants were assessed using standardized questionnaires, including the International Prostate Symptom Score (IPSS) for lower urinary tract symptoms (LUTS), the Sexual Health Inventory for Men (SHIM) and EHS (Erection Hardness Score) for erectile function, and the AMS (Aging Males Symptoms rating scale) for late onset hypogonadism. Endocrinological parameters, including dehydroepiandrosterone sulfate (DHEA-S), insulin-like growth factor 1 (IGF-1), total testosterone and cortisol levels, as well as metabolic factors, including hemoglobin A1c (HbA1c) and triglyceride level, were evaluated as potential confounders.
RESULTS: The patient age was 50.62±0.24 years. The analysis revealed significant associations between higher FIB-4 Index quintiles and worsening sexual function and LUTS. Among endocrine factors, DHEA-S and IGF-1 exhibited decreasing trends with higher FIB-4 Index values, whereas cortisol showed an increasing trend. Surprisingly, no significant association was observed between FIB-4 Index and testosterone levels. HbA1c increased, but triglycerides did not correlate with FIB-4. Multiple regression confirmed IPSS and SHIM scores were independently linked to the FIB-4 Index (p<0.05).
CONCLUSIONS: These findings highlight the importance of hepatic assessment in men with erectile dysfunction and LUTS, supporting a multidisciplinary approach to care.

Keywords:  Erectile dysfunction; Hormones; Liver fibrosis; Lower urinary tract symptoms; Metabolic syndrome

DOI:  https://doi.org/10.4111/icu.20250387
Psychoneuroendocrinology. 2025 Oct 28. pii: S0306-4530(25)00386-5. [Epub ahead of print]183 107663

Fetal Dehydroepiandrosterone from Hair Samples at Birth Predicts Language Development.

Michaela Reimann-Ayiköz, Jasmin Preiß, Eva Reisenberger, Cristina Florea, Monika Angerer, Manuel Schabus, Dietmar Roehm, Gesa Schaadt, Claudia Männel.

   OBJECTIVE: Sex hormones testosterone and estradiol have been related to children's language development. Expanding the focus on dehydroepiandrosterone (DHEA), which has not yet been considered as a biological marker of language ability, may provide novel insights, as emerging evidence suggests that fetal DHEA plays a critical role in the organization of the neonatal brain, potentially shaping later language development. The present study investigated whether fetal DHEA, compared to fetal testosterone, is associated with infant language development.
DESIGN AND METHODS: DHEA and testosterone concentrations were measured in newborn hair strands (n = 63) collected two weeks after birth, capturing fetal long-term hormone secretions during the third trimester of pregnancy. At six months of age, children's language abilities were assessed using the German version of the Bayley Scales of Infant Development.
RESULTS: Multiple linear regression analysis revealed fetal DHEA levels to be significantly associated with language abilities at six months of age in boys only, with lower DHEA levels corresponding to higher language scores. Control analyses assessing general cognitive abilities showed no association of fetal DHEA levels with infant cognitive function. Testosterone levels were not associated with language.
CONCLUSIONS: The current study identifies fetal DHEA levels extracted from newborn hair samples as a potential biological factor influencing infant language development in boys.

Keywords:  Biomarker; Fetal Dehydroepiandrosterone (DHEA); Fetal Testosterone; Hair Hormone Concentration; Language Development

DOI:  https://doi.org/10.1016/j.psyneuen.2025.107663